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Diseases usually are indicated by signs and symptoms. A sign is an objective manifestation of disease that can be determined by a physician; a symptom is subjective evidence of disease reported by the patient. Each disease entity has a constellation of signs and symptoms more or less uniquely its own; individual signs such as fever, however, may be found in a great number of diseases. Some of the common manifestations of disease—as they relate to an imbalance of normal homeostasis—are taken up in this section. They are covered more at length in the article diagnosis.

Fever is an abnormal rise in body temperature. It is most often a sign of infection but can be present whenever there is tissue destruction, as, for example, from a severe burn or when large amounts of tissue have died because of lack of blood supply. Body temperature is controlled by the thermostatic centre in the hypothalamus. Certain protein and polysaccharide substances are capable of raising the thermostat and causing a rise in body temperature. Fever is a highly significant indicator of disease.

An increase in the number of circulating phagocytic white blood cells (leukocytosis), is one of the more common manifestations of disease. The stimulus for such an event may be any inflammatory process in the body, such as is caused by bacteria, viruses, or any process that leads to the destruction of cells. Such leukocytosis is reflected in the white blood cell count, which may be substantially elevated above the normal upper value of 10,000 cells per cubic millimetre of blood.

The pulse rate is another easily obtainable and important piece of information. The heart rate varies with the level of physical activity: the heart beats faster during exercise and more slowly during rest. Persons who are physically active typically have a lower resting heart rate than sedentary individuals.. Moreover, an inappropriate heart rate (or pulse) can be indicative of disease. The heart rate increases in the feverish patient. A weak, rapid pulse rate may be a sign of severe blood loss or of disease within the heart itself. Irregularity of the pulse (arrhythmia) is an important indicator of heart malfunction.

The respiratory rate (rate of breathing) is modified by disease. Persons with fever have an increased respiratory rate (hyperventilation), which serves to lower body temperature (this rapid breathing is analogous to the panting of a dog). Hyperventilation is a common response to painful stress. Any condition leading to acidosis (lowering of body pH) similarly drives the respiratory rate upward. Diseases of the lungs—with the accompanying inability to oxygenate the blood adequately—have a similar effect.

Temperature, pulse, and respiratory rate—called the vital signs—may be important manifestations of disease. A fourth vital sign, blood pressure, is equally significant. Among other things, it indicates the amount of blood in circulation. A decrease in circulating blood volume, as is seen with severe bleeding, lowers the blood pressure and deprives the tissues of adequate blood flow. Reflexes are initiated that compensate for the reduced blood volume and blood pressure. The heart rate increases and compensates to some extent for the sudden reduction in blood volume and pressure; at the same time, peripheral blood vessels in such areas as the abdomen constrict, tending to divert the reduced blood volume to the more vital areas such as the brain and head. Unusual elevation of pressure (hypertension) is a disease by itself.